3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Ursolic Acid Derivatives as Potential Agents Against Acanthamoeba Spp.

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The current chemotherapy of Acanthamoeba keratitis relies on few drugs with low potential and limited efficacy, for all this there is an urgent need to identify new classes of anti- Acanthamoeba agents. In this regard, natural products play an important role in overcoming the current need and medicinal chemistry of natural products represents an attractive approach for the discovery and development of new agents. Ursolic acid, a natural pentacyclic triterpenoid compound, possesses a broad spectrum of activities including anti- Acanthamoeba. Herein, we report on the development by chemical transformation of an ursolic acid-based series of seven compounds (2–8), one of them reported for the first time. The structure-activity relationship (SAR) analysis of their anti- Acanthamoeba activity revealed that acylation/ether formation or oxidation enhances their biological profile, suggesting that the hydrophobic moiety contributes to activity, presumably by increasing the affinity and/or cell membrane permeability. These ursolic acid derivatives highlight the potential of this source as a good base for the development of novel therapeutic agents against Acanthamoeba infections.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Mitochondrial oxidative stress: implications for cell death.

          In addition to the established role of the mitochondria in energy metabolism, regulation of cell death has emerged as a second major function of these organelles. This seems to be intimately linked to their generation of reactive oxygen species (ROS), which have been implicated in mtDNA mutations, aging, and cell death. Mitochondrial regulation of apoptosis occurs by mechanisms, which have been conserved through evolution. Thus, many lethal agents target the mitochondria and cause release of cytochrome c and other pro-apoptotic proteins into the cytoplasm. Cytochrome c release is initiated by the dissociation of the hemoprotein from its binding to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and increases the level of soluble cytochrome c in the intermembrane space. Subsequent release of the hemoprotein occurs by pore formation mediated by pro-apoptotic Bcl-2 family proteins, or by Ca(2+) and ROS-triggered mitochondrial permeability transition, although the latter pathway might be more closely associated with necrosis. Taken together, these findings have placed the mitochondria in the focus of current cell death research.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment

            Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The importance of synthetic chemistry in the pharmaceutical industry

              Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.
                Bookmark

                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                23 August 2019
                September 2019
                : 8
                : 3
                : 130
                Affiliations
                [1 ]Instituto Universitario de Enfermedades Tropicalesy Salud Pública de Canarias, Universidad de La Laguna, Avda Francisco Sanchez s/n, Campus de Anchieta, 38271 La Laguna Tenerife, Islas Canarias, Espana
                [2 ]Laboratoire Matériaux-Molécules et Applications, University of Carthage, La Marsa Tunisia, Tunisia
                [3 ]Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Islas Canarias, Espana
                Author notes
                [* ]Correspondence: jpinero@ 123456ull.edu.es (J.E.P.); ignadiaz@ 123456ull.edu.es (I.A.J.)
                Author information
                https://orcid.org/0000-0001-6233-8224
                https://orcid.org/0000-0002-7698-2704
                Article
                pathogens-08-00130
                10.3390/pathogens8030130
                6789456
                31443577
                15976fa7-d821-4b0a-98a6-aff0fae3a0d4
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 August 2019
                : 21 August 2019
                Categories
                Article

                ursolic acid derivatives,acanthamoeba,chemotherapy,programmed cell death

                Comments

                Comment on this article